Abstract
Novel computational tools for swine vaccine development can expand the range of immunization approaches available to prevent economically devastating swine diseases and spillover events between pigs and humans. PigMatrix and EpiCC are two new tools for swine T cell epitope identification and vaccine efficacy analysis that have been integrated into an existing computational vaccine design platform named iVAX. The iVAX platform is already in use for the development of human vaccines, thus integration of these tools into iVAX improves and expands the utility of the platform overall by making previously validated immunoinformatics tools, developed for humans, available for use in the design and analysis of swine vaccines. PigMatrix predicts T cell epitopes for a broad array of class I and class II swine leukocyte antigen (SLA) using matrices that enable the scoring of sequences for likelihood of binding to SLA. PigMatrix facilitates the prospective selection of T cell epitopes from the sequences of swine pathogens for vaccines and permits the comparison of those predicted epitopes with “self” (the swine proteome) and with sequences from other strains. Use of PigMatrix with additional tools in the iVAX toolkit also enables the computational design of vaccines in silico, for testing in vivo. EpiCC uses PigMatrix to analyze existing or proposed vaccines for their potential to protect, based on a comparison between T cell epitopes in the vaccine and circulating strains of the same pathogen. Performing an analysis of T cell epitope relatedness analysis using EpiCC may facilitate vaccine selection when a novel strain emerges in a herd and also permits analysis of evolutionary drift as a means of immune escape. This review of novel computational immunology tools for swine describes the application of PigMatrix and EpiCC in case studies, such as the design of cross-conserved T cell epitopes for swine influenza vaccine or for African Swine Fever. We also describe the application of EpiCC for determination of the best vaccine strains to use against circulating viral variants of swine influenza, swine rotavirus, and porcine circovirus type 2. The availability of these computational tools accelerates infectious disease research for swine and enable swine vaccine developers to strategically advance their vaccines to market.
Highlights
Pigs are an important component of the agricultural economy worldwide and are an important contributor to protein intake for populations living in developed and developing world economies
To estimate the relationship between pathogen sequences based on their putative T cell epitope content and predict crossprotection potential, we developed the T cell Epitope Content Comparison tool (EpiCC) which facilitates sequence pairwise comparison based on epitope content rather than sequence identity [42]
Using iVAX, we developed a T cell-directed African swine fever (ASF) vaccine composed of swine major hisotocompatability complex (MHC) class I and class II epitopes conserved across 21 European, Asian and African isolates covering genotypes I, II, IX, and X
Summary
Pigs are an important component of the agricultural economy worldwide and are an important contributor to protein intake for populations living in developed and developing world economies. Overall, using the pocket profile method for SLA, and defined binding preferences from HLA, shows promise for developing T cell epitope prediction tools for pigs.
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